Preparation of human serum albumin nanoparticles for cancer therapy

As BH4 is easily oxidized and AZD3965 is toxic to the heart, the two drugs were separately encapsulated into human serum albumin nanoparticles (HSA NPs) to improve their efficacy and safety profile. <br><br>Initially, to load our drugs into the optimal human serum albumin (HSA) nanoparticles, empty HSA NPs were prepared by the desolvation technique. The effects of parameters in the formulation were systematically investigated.

The physicochemical properties of the prepared HSA NPs (size, polydispersity, and zeta potential) were evaluated. The optimized desolvation method demonstrated that the size of HSA NPs can be controlled between 100 and 200 nm, with a narrow polydispersity and negative surface charge. <br><br>Then, BH4-loaded HSA NPs were prepared using the desolvation method. However, the encapsulation efficiency of BH4 was low.

Therefore, further work is needed to improve BH4 loading into HSA NPs.<br><br>Finally, nonosized AZD3965-loaded HSA NPs with 28% encapsulation efficiency were successfully prepared using the desolvation method, enabling in vitro and in vivo testing. Promisingly, extracellular lactate levels were significantly reduced in cancer cells after treatment. In vitro testing, the intravenous injection of AZD3965 or AZD3965-loaded HSA NPs inhibited tumour growth in mic. <br><br><i>Thesis is embargoed until 31 December 2026.</i>